Recent research findings suggest that endometriosis may be related to select environmental agents (e.g., dioxin). In particular, a significant correlation was reported for TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and severity of endometriosis in a colony of rhesus monkeys. As yet, little study of the relationship between exposure to halogenated organics and endometriosis in humans has been undertaken and that serves as the impetus for study. The long-term objectives of this study is to assess whether exposure to persistent halogenated organics, including dioxin, is involved in the aetiology of endometriosis. Five specific objectives have been developed: 1) to identify and elicit the cooperation of women with newly diagnosed endometriosis (cases) and women free of disease (controls); 2) to compare measured levels of persistent halogenated organics in fat and serum between cases and controls; 3) to assess biomarkers of exposure and effect related to dioxin-like compounds by measuring levels of cytochrome P450 1A1 (CYP1A1) and 1B1 (CYP1B1) in uterine endometrium and ectopic endometrial implants; 4) to validate the biomarkers by assessing CYP1A1 and CYP1B1 in tissues from the original colony of rhesus monkeys with known exposures to TCDD and laparoscopically-confirmed endometriosis; and 5) to assess endometriosis risk as a function of both biomarkers expression and measured exposure status. A case-control study design will be used to identify and recruit cases and controls from the population of women undergoing laparoscopic surgery at one University-affiliated hospital. Fifty women with newly-diagnosed endometriosis and 100 age-matched women undergoing interval tubal ligations and who are found to be free of endometriosis will comprise the study sample. A standardized operative alpha-sequencing inspection of the pelvis will be performed by surgeons for all women. All laparoscopic-confirmed endometriosis will be staged according to the revised American Fertility Society classification. Standardized in-home interviews will be conducted with all women; serum will be collected from women as well. Approximately 5 grams of omentum fat will be taken at the time of laparoscopy from all women for comprehensive exposure assessment. Among cases, biopsies will be taken from the endometrium and ectopic endometrial implants for biomarker assessment. The successful completion of this study will be enhanced by its multidisciplinary design, attention to sound epidemiologic methods and utilization of state-of-the-art exposure, biomarker and surgical techniques. As such, the proposed study shall help clarify the mechanisms underlying the development of endometriosis.